This project is a study of mechanisms involved in the pulmonary toxicity of paraquat, an herbicide extensively used in agriculture. In rats, the 48-hr mortality from paraquat ip was increased by sc injection of a single dose of a beta adrenergic agonist (1-isoproterenol, salbutamol, carbuterol, or fenoterol). Pretreatment with d1-propranolol, 1-propranolol, or bunolol, all beta blocking agents, completely blocked isoproterenol-induced potentiation of paraquat toxicity. Other beta blocking agents and d-propranolol were less or not effective. Isoproterenol-induced potentiation of paraquat toxicity and its blockade by propranolol were also demonstrated in mice. C14-labeled paraquat, N-methylnicotinamide (NMN), or p-aminohippuric acid (PAH) was injected into the tail vein of rats and plasma disappearance of radioactivity was followed in blood from the retro-orbital sinus. Since isoproterenol (0.3 mg/kg), injected sc at the same time as the test compound, reduced the clearance of both basic (paraquat and NMN) and acidic (PAH) compounds, it must have reduced renal blood flow. The reduced clearance contributed at least partially to the increased toxicity of paraquat. There was no clear relationship between the effect of a drug on paraquat mortality and its effect on paraquat uptake by lung slices in vitro. We have failed to detect, in vitro or in vivo, production of the superoxide free radical by paraquat.